Before the appearance of the first oral treatment, male sexual impotence was treated by intracavernous injections and other means, due to, in particular, doubts stemming from adverse reactions that oral administration could cause in humans. Papaverine and pentoxifylline, for example, were used in the treatment of erectile dysfunction by intracavernous injections. Other means of treatment, less efficient, were, for example, psychotherapies and surgical implants.
Oral treatment is most acceptable by man, and it emerged from clinical research using inhibitors of cGMP-PDE, more specifically, PDE-5. The precursor of these compounds was 5-[2-ethoxy-5-(4-methylpiperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, or sildenafil, with vasodilator properties and potentiates the effects of nitric oxide. Sildenafil is the active ingredient of the medicine Viagra®.
Later, other inhibitor compounds of PDE-5 were developed and are cited in numerous publications of technical literature, as well as patent publications, such as vardenafil, the active ingredient of the medicine Levitra®, and tadalafil, the active ingredient of the medicine Clalis®.
The compounds of the present invention, the derivatives of 6,7-dihydro-3H-oxazolo[3,4-a]pyrazine-5,8-dione, are also inhibitors of the enzyme phosphodiesterase type 5 (PDE-5).